US 12,258,349 B2
Anti-viral drug
Pavel Vladimirovich Sorokin, Novouralsk (RU); and David Edmund Thorne, Oberterzen (CH)
Assigned to DORING INTERNATIONAL GMBH, Oberterzen (CH)
Filed by DORING INTERNATIONAL GMBH, Oberterzen (CH)
Filed on Jun. 1, 2022, as Appl. No. 17/830,158.
Application 17/830,158 is a division of application No. 16/862,290, filed on Apr. 29, 2020, granted, now 11,370,797.
Application 16/862,290 is a continuation of application No. 16/079,954, abandoned, previously published as PCT/EP2017/054423, filed on Feb. 24, 2017.
Claims priority of application No. 16157238 (EP), filed on Feb. 24, 2016.
Prior Publication US 2022/0298164 A1, Sep. 22, 2022
Int. Cl. C07D 487/04 (2006.01)
CPC C07D 487/04 (2013.01) 13 Claims
 
1. A process for manufacture of an antiviral compound of formula (I) or a pharmaceutically acceptable salt thereof

OG Complex Work Unit Chemistry
wherein
R1 is an alkyl group having 1 to 12 carbon atoms which is optionally substituted by a halogen atom or hydroxyl group, a cycloalkyl group having 3 to 12 carbon atoms which is optionally substituted by a halogen atom or hydroxyl group, an aryl group, an alkylaryl group, or a cycloheteroalkyl group having 3 to 12 carbon atoms,
comprising steps of:
(a) diazotizing a compound of formula (II):

OG Complex Work Unit Chemistry
wherein R2 is hydrogen, thereby forming a diazonium compound of formula (III) or a pharmaceutically acceptable salt thereof:

OG Complex Work Unit Chemistry
(b) condensing the compound of formula (III) or a pharmaceutically acceptable salt thereof with at least one α-nitroester of formula (IV) thereby forming 7 mercapto-3-nitro-1,2,4-triazolo [5,1-c]-1,2,4-triazin-4 (1H)-one or a pharmaceutically acceptable salt thereof:

OG Complex Work Unit Chemistry
wherein
R3 is:
(CO)—OR5, wherein R5 is an alkyl group having 1 to 24 carbon atoms which is optionally substituted by a hydroxyl group, an amino group, a halogen atom, an aryl group, or an aralkyl group; or
(CO)—R6, wherein R6 is an alkyl group having 1 to 12 carbon atoms which is optionally substituted by a hydroxyl group, an amino group, a halogen atom, an aryl group, or an aralkyl group, and
R4 is an alkyl group having 1 to 24 carbon atoms which is optionally substituted by a hydroxyl group, an amino group, a halogen atom, an aryl group, or an aralkyl group; or an alkenyl group; and
(c) contacting 7 mercapto-3-nitro-1,2,4-triazolo [5,1-c]-1,2,4-triazin-4(1H)-one, or a pharmaceutically acceptable salt thereof, with an alkylating agent of formula (V), which is R1—X, or formula (VI), which is R1—Z, in a suitable solvent, wherein X is a halogen atom or an oxygen containing functional group selected from tosylate (OTs) and trimethylsiloxy (OTMS), and Z is a sulfate group or a carbonate group.